IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-46408-3.html
   My bibliography  Save this article

Immunopeptidomics-based identification of naturally presented non-canonical circRNA-derived peptides

Author

Listed:
  • Humberto J. Ferreira

    (University of Lausanne
    Centre Hospitalier Universitaire Vaudois
    Agora Cancer Research Centre)

  • Brian J. Stevenson

    (University of Lausanne
    Agora Cancer Research Centre
    University of Lausanne)

  • HuiSong Pak

    (University of Lausanne
    Centre Hospitalier Universitaire Vaudois
    Agora Cancer Research Centre)

  • Fengchao Yu

    (University of Michigan)

  • Jessica Almeida Oliveira

    (University of Lausanne
    Centre Hospitalier Universitaire Vaudois
    Agora Cancer Research Centre)

  • Florian Huber

    (University of Lausanne
    Centre Hospitalier Universitaire Vaudois
    Agora Cancer Research Centre)

  • Marie Taillandier-Coindard

    (University of Lausanne
    Centre Hospitalier Universitaire Vaudois
    Agora Cancer Research Centre)

  • Justine Michaux

    (University of Lausanne
    Centre Hospitalier Universitaire Vaudois
    Agora Cancer Research Centre)

  • Emma Ricart-Altimiras

    (University of Lausanne
    Centre Hospitalier Universitaire Vaudois
    Agora Cancer Research Centre)

  • Anne I. Kraemer

    (University of Lausanne
    Centre Hospitalier Universitaire Vaudois
    Agora Cancer Research Centre)

  • Lana E. Kandalaft

    (University of Lausanne
    Centre Hospitalier Universitaire Vaudois
    Agora Cancer Research Centre
    Centre Hospitalier Universitaire Vaudois)

  • Daniel E. Speiser

    (Centre Hospitalier Universitaire Vaudois)

  • Alexey I. Nesvizhskii

    (University of Michigan
    University of Michigan)

  • Markus Müller

    (University of Lausanne
    Centre Hospitalier Universitaire Vaudois
    Agora Cancer Research Centre
    University of Lausanne)

  • Michal Bassani-Sternberg

    (University of Lausanne
    Centre Hospitalier Universitaire Vaudois
    Agora Cancer Research Centre
    Centre Hospitalier Universitaire Vaudois)

Abstract

Circular RNAs (circRNAs) are covalently closed non-coding RNAs lacking the 5’ cap and the poly-A tail. Nevertheless, it has been demonstrated that certain circRNAs can undergo active translation. Therefore, aberrantly expressed circRNAs in human cancers could be an unexplored source of tumor-specific antigens, potentially mediating anti-tumor T cell responses. This study presents an immunopeptidomics workflow with a specific focus on generating a circRNA-specific protein fasta reference. The main goal of this workflow is to streamline the process of identifying and validating human leukocyte antigen (HLA) bound peptides potentially originating from circRNAs. We increase the analytical stringency of our workflow by retaining peptides identified independently by two mass spectrometry search engines and/or by applying a group-specific FDR for canonical-derived and circRNA-derived peptides. A subset of circRNA-derived peptides specifically encoded by the region spanning the back-splice junction (BSJ) are validated with targeted MS, and with direct Sanger sequencing of the respective source transcripts. Our workflow identifies 54 unique BSJ-spanning circRNA-derived peptides in the immunopeptidome of melanoma and lung cancer samples. Our approach enlarges the catalog of source proteins that can be explored for immunotherapy.

Suggested Citation

  • Humberto J. Ferreira & Brian J. Stevenson & HuiSong Pak & Fengchao Yu & Jessica Almeida Oliveira & Florian Huber & Marie Taillandier-Coindard & Justine Michaux & Emma Ricart-Altimiras & Anne I. Kraeme, 2024. "Immunopeptidomics-based identification of naturally presented non-canonical circRNA-derived peptides," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46408-3
    DOI: 10.1038/s41467-024-46408-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-46408-3
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-46408-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Haoqing Shen & Omer An & Xi Ren & Yangyang Song & Sze Jing Tang & Xin-Yu Ke & Jian Han & Daryl Jin Tai Tay & Vanessa Hui En Ng & Fernando Bellido Molias & Priyankaa Pitcheshwar & Ka Wai Leong & Ker-Ka, 2022. "ADARs act as potent regulators of circular transcriptome in cancer," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Thomas B. Hansen & Trine I. Jensen & Bettina H. Clausen & Jesper B. Bramsen & Bente Finsen & Christian K. Damgaard & Jørgen Kjems, 2013. "Natural RNA circles function as efficient microRNA sponges," Nature, Nature, vol. 495(7441), pages 384-388, March.
    3. Chloe Chong & Markus Müller & HuiSong Pak & Dermot Harnett & Florian Huber & Delphine Grun & Marion Leleu & Aymeric Auger & Marion Arnaud & Brian J. Stevenson & Justine Michaux & Ilija Bilic & Antje H, 2020. "Integrated proteogenomic deep sequencing and analytics accurately identify non-canonical peptides in tumor immunopeptidomes," Nature Communications, Nature, vol. 11(1), pages 1-21, December.
    4. Vadim Demichev & Lukasz Szyrwiel & Fengchao Yu & Guo Ci Teo & George Rosenberger & Agathe Niewienda & Daniela Ludwig & Jens Decker & Stephanie Kaspar-Schoenefeld & Kathryn S. Lilley & Michael Mülleder, 2022. "dia-PASEF data analysis using FragPipe and DIA-NN for deep proteomics of low sample amounts," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    5. Kevin L. Yang & Fengchao Yu & Guo Ci Teo & Kai Li & Vadim Demichev & Markus Ralser & Alexey I. Nesvizhskii, 2023. "MSBooster: improving peptide identification rates using deep learning-based features," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    6. Xiaojuan Fan & Yun Yang & Chuyun Chen & Zefeng Wang, 2022. "Pervasive translation of circular RNAs driven by short IRES-like elements," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Wei Hu & Yangjun Wu & Qili Shi & Jingni Wu & Deping Kong & Xiaohua Wu & Xianghuo He & Teng Liu & Shengli Li, 2022. "Systematic characterization of cancer transcriptome at transcript resolution," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    8. Fengchao Yu & Guo Ci Teo & Andy T. Kong & Klemens Fröhlich & Ginny Xiaohe Li & Vadim Demichev & Alexey I. Nesvizhskii, 2023. "Analysis of DIA proteomics data using MSFragger-DIA and FragPipe computational platform," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Yi Yang & Qun Fang, 2024. "Prediction of glycopeptide fragment mass spectra by deep learning," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    2. Hui Peng & He Wang & Weijia Kong & Jinyan Li & Wilson Wen Bin Goh, 2024. "Optimizing differential expression analysis for proteomics data via high-performing rules and ensemble inference," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Charlotte Adams & Wassim Gabriel & Kris Laukens & Mario Picciani & Mathias Wilhelm & Wout Bittremieux & Kurt Boonen, 2024. "Fragment ion intensity prediction improves the identification rate of non-tryptic peptides in timsTOF," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    4. Fengchao Yu & Guo Ci Teo & Andy T. Kong & Klemens Fröhlich & Ginny Xiaohe Li & Vadim Demichev & Alexey I. Nesvizhskii, 2023. "Analysis of DIA proteomics data using MSFragger-DIA and FragPipe computational platform," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Eduardo Vieira de Souza & Angie L. Bookout & Christopher A. Barnes & Brendan Miller & Pablo Machado & Luiz A. Basso & Cristiano V. Bizarro & Alan Saghatelian, 2024. "Rp3: Ribosome profiling-assisted proteogenomics improves coverage and confidence during microprotein discovery," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    6. Wojciech Barczak & Simon M. Carr & Geng Liu & Shonagh Munro & Annalisa Nicastri & Lian Ni Lee & Claire Hutchings & Nicola Ternette & Paul Klenerman & Alexander Kanapin & Anastasia Samsonova & Nicholas, 2023. "Long non-coding RNA-derived peptides are immunogenic and drive a potent anti-tumour response," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Yu Dong & Qian Gao & Yong Chen & Zhao Zhang & Yanhua Du & Yuan Liu & Guangxiong Zhang & Shengli Li & Gaoyang Wang & Xiang Chen & Hong Liu & Leng Han & Youqiong Ye, 2023. "Identification of CircRNA signature associated with tumor immune infiltration to predict therapeutic efficacy of immunotherapy," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Wai Tuck Soh & Hanna P. Roetschke & John A. Cormican & Bei Fang Teo & Nyet Cheng Chiam & Monika Raabe & Ralf Pflanz & Fabian Henneberg & Stefan Becker & Ashwin Chari & Haiyan Liu & Henning Urlaub & Ju, 2024. "Protein degradation by human 20S proteasomes elucidates the interplay between peptide hydrolysis and splicing," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    9. Guilherme Reis-de-Oliveira & Victor Corasolla Carregari & Gabriel Rodrigues dos Reis de Sousa & Daniel Martins-de-Souza, 2024. "OmicScope unravels systems-level insights from quantitative proteomics data," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    10. Bin Li & Wen-Wu Bai & Tao Guo & Zhen-Yu Tang & Xue-Jiao Jing & Ti-Chao Shan & Sen Yin & Ying Li & Fu Wang & Mo-Li Zhu & Jun-Xiu Lu & Yong-Ping Bai & Bo Dong & Peng Li & Shuang-Xi Wang, 2024. "Statins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    11. Georges Bedran & Daniel A. Polasky & Yi Hsiao & Fengchao Yu & Felipe Veiga Leprevost & Javier A. Alfaro & Marcin Cieslik & Alexey I. Nesvizhskii, 2023. "Unraveling the glycosylated immunopeptidome with HLA-Glyco," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    12. Ting-Ting He & Yun-Fan Xu & Xiang Li & Xia Wang & Jie-Yu Li & Dan Ou-Yang & Han-Sen Cheng & Hao-Yang Li & Jia Qin & Yu Huang & Hai-Yan Wang, 2023. "A linear and circular dual-conformation noncoding RNA involved in oxidative stress tolerance in Bacillus altitudinis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    13. Xiujuan Lei & Wenxiang Zhang, 2019. "BRWSP: Predicting circRNA-Disease Associations Based on Biased Random Walk to Search Paths on a Multiple Heterogeneous Network," Complexity, Hindawi, vol. 2019, pages 1-12, November.
    14. Jennifer G. Abelin & Erik J. Bergstrom & Keith D. Rivera & Hannah B. Taylor & Susan Klaeger & Charles Xu & Eva K. Verzani & C. Jackson White & Hilina B. Woldemichael & Maya Virshup & Meagan E. Olive &, 2023. "Workflow enabling deepscale immunopeptidome, proteome, ubiquitylome, phosphoproteome, and acetylome analyses of sample-limited tissues," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    15. Samuel Rivero-Hinojosa & Melanie Grant & Aswini Panigrahi & Huizhen Zhang & Veronika Caisova & Catherine M. Bollard & Brian R. Rood, 2021. "Proteogenomic discovery of neoantigens facilitates personalized multi-antigen targeted T cell immunotherapy for brain tumors," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    16. Karsten Suhre & Guhan Ram Venkataraman & Harendra Guturu & Anna Halama & Nisha Stephan & Gaurav Thareja & Hina Sarwath & Khatereh Motamedchaboki & Margaret K. R. Donovan & Asim Siddiqui & Serafim Batz, 2024. "Nanoparticle enrichment mass-spectrometry proteomics identifies protein-altering variants for precise pQTL mapping," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    17. Zhen Dong & Wenhao Jiang & Chunlong Wu & Ting Chen & Jiayi Chen & Xuan Ding & Shu Zheng & Kiryl D. Piatkevich & Yi Zhu & Tiannan Guo, 2024. "Spatial proteomics of single cells and organelles on tissue slides using filter-aided expansion proteomics," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    18. Mateja Rybiczka-Tešulov & Oxana Garritsen & Morten T. Venø & Laura Wieg & Roland van Dijk & Karim Rahimi & Andreia Gomes-Duarte & Marina de Wit & Lieke L. Haar & Lars Michels & Nicky C. H. van Kronenb, 2024. "Circular RNAs regulate neuron size and migration of midbrain dopamine neurons during development," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    19. Roberta Piras & Emily Y. Ko & Connor Barrett & Marco Simone & Xianzhi Lin & Marina T. Broz & Fernando H. G. Tessaro & Mireia Castillo-Martin & Carlos Cordon-Cardo & Helen S. Goodridge & Dolores Vizio , 2022. "circCsnk1g3- and circAnkib1-regulated interferon responses in sarcoma promote tumorigenesis by shaping the immune microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    20. Karl K. Krull & Syed Azmal Ali & Jeroen Krijgsveld, 2024. "Enhanced feature matching in single-cell proteomics characterizes IFN-γ response and co-existence of cell states," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46408-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.